Click here to load reader
Holder 1
The Groundbreaking Career as aResearch Associate in Cancer Immunology
Report• Ashley Holder • Grade 12 •
• Ms. Mary Glodowski • Juanita High School •• February 28, 2003 •
• Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
Holder 2
Table of Contents
Report
Report Page 3
Bibliography Page
13
Journal
Notes Page 16
Interview Page 18
Impressions Page 19
• Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
Holder 3
Research Associate in Cancer Immunology
A research associate is generally in charge of research and development on
projects, usually with others. He observes, analyzes, and interprets results. Basically a
research associate is knowledgeable in his area of study and can do anything involving
research that includes analyzing data and results, preparing technical reports,
participating in scientific conferences, or even conducting experiments.
According to Jeff Johnson, Senior Research Associate at Corixa Corporation,
Research Associates are the foundation for the development of immunological and other
drug developments. They provide their supervisors with the results from their own
experiments. Their reports and interpretations become the information that their
supervisors use to determine where to go next in the drug’s development.
To be a research associate in cancer immunology, one must have a college degree
in biological science, chemistry, immunology, or molecular biology. It is helpful to have
computer skills. Also, one must have experience with radioisotopes, tissue culture,
column chromatography, protein determinations, immunoassay, and western blobs.
Job responsibilities actually vary from company to company, but generally include the
preparation and isolation of tumor antigens from specimens. One must also perform
biological analysis and immunological assays in order to monitor antigens. He or she
may also research and develop immunological assays using reagents. Other
responsibilities might include the recording and logging of lab equipment as required for
the Cancer Laboratory Practices (GLP).
While on the surface, a typical workday lasts from 9 AM to 5 PM, a typical
research associate can spend untold hours in the lab. One would not blink twice to hear
• Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
Holder 4
that an associate stayed hours after “closing” to finish an experiment or to complete a
report. At least half of Jeff Johnson’s workday is data entry and computer analysis. He
also spends a lot of time preparing and carrying out experiments and then going to
meetings to present his findings.
A research associate can become a senior research associate when he or she has
experience for a number of years as a member of a clinical team conducting studies
(Phase I-Phase IV) according to federal regulations and ICH guidelines. He or she, as a
senior research assistant, is responsible for either writing of supervising someone writing
the clinical reports or documents for publication. In most instances, to become a
Supervisor, one must have a Ph.D. However, new policies at Corixa allow research
associates to become supervisors, even if they do not have a Ph.D. They must go
through an extensive application and interview process.
Salaries for a research associate range from about 20 dollars an hour to nearly 50
dollars an hour. The huge discrepancy in wage is based mainly on experience and
education level. Also, company and area of the country play roles in salary
determination.
Mentorship with a Research Associate
Getting into the Corixa Corporation building was a challenge; security was taken
seriously. The “Average Joe” could not walk into the building without first calling the
security guard. Once inside, I had to check in with the receptionist on the second floor,
getting a visitor pass in order to continue into Corixa. About five minutes later, Jeff
Johnson came down to show me the way to his lab/work station. It was located in a huge
• Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
Holder 5
room with 20 other research associates. Each had his or her own glorified cubicle style
station. The general atmosphere was relaxed. Each scientist was working on his or her
own project, mumbling to his or her self about one thing or another.
Jeff Johnson, as I learned, had been a Corixa for just over 5 years. He attended
Seattle Pacific University and earned a Bachelors of Science in Biology and
Environmental Studies with a Chemistry Minor. Just out of college, he first did research
at Fred Hutchinson Cancer Research Center from 1993-1997. There he was able to
acquire the invaluable skills needed as a research associate. Although his experience at
Fred Hutchinson Cancer Research Center was precious, he decided to work at Corixa
Corporation in 1997. According to Jeff Johnson, many people right out of college do
research at the Fred Hutchinson Cancer Research Center to gain the experience needed to
get a job at a private company. Fred Hutch is government run. This brought many
obstacles into his research; the first of which being finances. Supplies at the Fred
Hutchinson Cancer Research Center were budgeted. All supplies were bought as cheaply
as possible. Also, salary was significantly less at The Hutch. Now at Corixa, Jeff
Johnson no longer has to pay as close attention to the price of supplies. Except for
expensive machinery, he can order what he needs without worrying about money.
Taking a tour of Corixa was interesting. I was shown different floors, each floor
specializing in its own area of cancer treatment development. For instance, on the upper
floor, research associates and other scientists were working on the purification of certain
samples to be run in experiments. I was then shown where all the samples are kept and
where the CHO was being produced and stored. I found it funny to look at lab areas and
see all of the open container violations that I would be marked down for during labs.
• Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
Holder 6
When I asked Mr. Johnson about it he laughed and said that he should be keeping
everything more clean, but when you’re in the real world of science, such small
violations are not as important. He made it clear however, that certain experiments
required sterile environments in which he follows impeccable lab procedure.
Jeff Johnson was extremely knowledgeable. The majority of time at Corixa
(about two hours), was spent listening to him explain how certain equipment was used
and then his explanation of how antibodies were used to treat cancer. He even talked
about certain genes and DNA that Mrs. Glowdowski had taught the class weeks earlier.
Because of Biotechnology Class and earlier research, I was able to understand the
majority of Mr. Johnson’s technical jargon.
Later in the afternoon, I was given the opportunity to see the results of one of Jeff
Johnson’s experiments completed the previous day. This particular experiment had to do
with narrowing down a certain characteristic found in a certain kind of cancer, but for
confidentiality reasons and my comprehension level, he was not able to go into much
more detail. He did, however, explain to me how to read the chart in which the results
were reflected. The graph looked like two mountains, one representing a control, the
other representing the effect of a substance on cancer cells. It showed at what point a
cancer cell died. Unfortunately, the substance had little effect on the cancer cells. After
the depressing news, I learned that it is rare, in Jeff Johnson’s stage of development, for
results of an experiment to be successful. Mr. Johnson summarized the hope and then
disappointment best when he said, “You know, 95% of our experiments are unsuccessful
during the year, but it’s the 5%—the one or two successful experiments, that keep you
going.”
• Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
Holder 7
Leaving Corixa, I was amazed at where Jeff Johnson’s heart was. He is not in
cancer research for money or fame. He loves his job because of the potential impact he
can have on someone’s life. That is where a true scientist’s priorities should be!
So what is Cancer?
Cancer is a condition, occuring in both plants and animals, when cells multiply
too quickly, destroying healthy tissue. In humans, the majority of reported cancer cases
are in middle-aged to elderly adults. The most effected areas of the body include the
skin, digestive organs, the lungs, the prostate gland, and the female’s breasts. It occurs
when chemicals that direct cell growth are damaged, resulting in cells multiplying out of
control. Doctors and scientists classify the type of cancer by where it is located in the
body and the tissue of origin.
There are two kinds of cancer classified as carcinoma and sarcoma. Carcinoma is
the more common of the two. It develops in the epithelial tissue. The epithelial tissue is
the outer layer of skin and the lining of the surfaces of the internal body and organs. The
second kind of cancer, sarcoma, develops in connective tissues.
There are also two kinds of genes that control cell growth and division: proto-
oncogenes and suppressor genes. Proto-oncogenes promote cell growth and divisions
while suppressor genes limit the amount of cell growth. In a perfect scenario, the proto-
oncogenes and the suppressor genes check each other. However, when proto-oncogenes
are damaged, and overactive form called oncogene can take over. The suppressor genes
are damaged, they lose the ability to stop cell multiplication.
• Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
Holder 8
Traditional Cancer Treatments
Surgery, radiation therapy, and drug therapy are the primary treatments for cancer
today. With surgery doctors remove the tumor and possibly the healthy tissue around it
to prevent spread. An excellent example of this procedure is the mastectomy. When a
mastectomy is preformed, the surgeon takes not only the tumor, but also the surrounding
breast. A major drawback of surgery is the invasiveness needed to be successful and the
recovery time. Also, as in the case of mastectomies, psychological effects can take years
to overcome.
Radiation therapy uses x-rays or other particles from radioactive substances like
cobalt and radium. While this form of treatment kills the cancerous cells, it also destroys
healthy cells. So, to be effective enough to be beneficial to the patient, radiation therapy
must kill more cancer cells than the normal cells. New machines are being used now that
target the cancer cells more precisely, thus reducing the number of normal cells
damaged. These machines are called the Super Voltage X-Ray and the Cobalt Bomb.
Drug therapy, also known as chemotherapy, is the idea that a drug can target
rapidly growing abnormal cells. The theory is good, however, blood-forming cells, hair-
forming cells, and even the cells lining the intestinal tract are rapidly reproducing.
Chemotherapy does not discriminate against healthy cells and cancerous cells—it
destroys both as long as they multiply quickly. So, some of the side effects of
chemotherapy are hair-loss (when hair-forming cells are killed), nausea and vomiting
(from destroying the cells lining the intestines), and infection and anemia (when the
blood-forming cells are destroyed).
• Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
Holder 9
Another kind of therapy called multimodality therapy combines treatments
together. For instance, a surgery followed by chemotherapy. The positive side of such
combinations is that it can destroy undetected cancer cells in other areas of the body.
A New Form of Treatment
More recently, researchers have found that there are biological response modifiers
that can accomplish two different objectives: the first being to increase the body’s own
ability to fight the cancer by using immunology and the second is to increase the body’s
ability to withstand aggressive drug treatments.
One promising type of a biological response modifier is the monoclonal antibody.
Antibodies, which are disease fighting proteins, are made by the thousand by the B cell, a
white blood cell. They circulate via the blood stream and attach themselves to antigens.
When the antibody attaches to the antigen, it acts as a marker essentially alerting the
immune system that the cell is infected and must be destroyed. Monoclonal antibodies
can be made in a laboratory by combining a cancer cell with a B-cell. This produces the
antibodies that attach to the cancer, alerting the immune system to destroy the remaining
cancerous cell. The positive impact of the monoclonal antibody is that it can successfully
target a cancer cell without destroying the healthy cells surrounding it.
Another biological modifier is the interferon. An interferon is a protein that is
produced by cells to resist infection brought about by viruses. In some studies it has
been shown to prevent the reappearance of cancer.
A third kind of biological modifier is interleukin-2, a protein released by some
white blood cells that helps to support the growth of other white blood cells. In some
• Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
Holder 10
kidney cancer patients, interleukin has stimulated the growth of white blood cells that kill
cancerous cells.
Cancer Immunology Out on the Market Today
Herceptin was the first antibody based cancer therapy. It is used to treat HER-2
driven metastatic breast cancer. Herceptin is able to bind to the surface of the tumor
cells. This, in turn, blocks cell growth so that the cancer cells can no longer multiply at
the unhealthy rate. When it attaches to the HER-2 proteins, natural killer (NK) cells then
attach to the Herceptin. This allows the cell to be detected as abnormal and thus
destroyed by the immune system. Chemotherapy can also be combined with Herceptin
to make a more powerful treatment. The chemotherapy destroys the DNA in the tumors,
then Herceptin stops the cells from healing themselves. This causes them to die and the
tumor’s growth to slow down drastically.
Another drug, RITUXAN, is out on the market that treats patients who have B-
cell non-Hodgkin’s Lymphoma. It was the first monoclonal antibody (MAb) approved
for the treatment of cancer in the United States of America. Rituxan effectively binds to
the surface of the CD20 antigen found on the surface of normal and malignant B cells.
From there, it recruits the body's natural defenses to attack and kill the marked B cells.
Stem cells in bone marrow lack the CD20 antigen so this form of treatment allows
healthy B cells to regenerate after treatment and return to normal levels within several
months.
New Drugs Being Developed by Corixa
• Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
Holder 11
Melacine is currently in phase III development. It is composed of broken cells
from two human melanoma cell lines mixed with Detox adjuvant, which activate the
immune system through vaccination. In studies conducted around the country by the
Southwest Oncology Group, the Melacine vaccine had demonstrated that it prolongs the
time in relapse-free survival in patients with stage II melanoma as compared to those
who were not treated with adjuvant therapy. The study included 689 patients chosen at
random from 148 sites. This trial is the largest study of cancer vaccine completed to
date. In order for the FDA to approve Melacine in the United States, it must go through a
second phase III clinical trial.
Melacine could potentially have a huge impact on skin cancer survival.
According to the American Cancer Society, skin cancer is the most common out of all
the cancers. Melanoma, a highly lethal form of skin cancer, accounts for only 4 percent
of skin cancers, yet it accounts for 79 percent of skin cancer deaths.
Another new drug being developed by Corixa is BEXXAR. BEXXAR combines
the ideas of radiology and monoclonal antibodies into non-Hodgkin’s lymphoma. NHL
is a blood-borne cancer of the immune system. The monoclonal anti-body binds to a
specific protein found on the B-cells. It marks the cancer cell to be destroyed by the
immune system. At the same time, a radioisotope can target its radiation to the tumor
cells so that fewer healthy, normal cells are damaged.
The National Cancer Institute estimates that NHL in the United States alone
affects over 300,000 people. That number continues to grow. In fact, since the early
1970’s, the rate of NHL occurrence has grown by 80%. On December 17, 2002, Corixa
received strong praise from the Oncologic Drugs Advisory Committee. They
• Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
Holder 12
unanimously voted that BEXXAR was effective in the treatment of chemotherapy-
relapsed and refractory low-grade NHL. The date in which the FDA will finish its
review of BEXXAR is on May 2, 2003.
Conclusion
Cancer treatment is headed in a positive new direction. With companies, such as
Corixa, developing innovative ways to treat and perhaps cure cancer, one stands in awe
of all the possibilities. It makes one wonder what the next innovation will be. The
number of people potentially affected by these new antibody treatments is staggering.
These new methods of therapy are able to reduce the amount of negative side effects of
traditional treatments. As a Research Associate in Cancer Immunology, one is at the
groundwork of these exciting new technologies. Not only is this career thrilling, it is
filled with untold rewards.
Bibliography
“Cancer.” World Book. 16th ed. 2002This was a credible source because the encyclopedia is turned to by many for its unbiased definitions. I used the encyclopedia to gain a basic knowledge of cancer.
Yount, Lisa. “Radiation and Chemotherapy” Cancer. Lucent Books, 1999.This was a credible source because it was unbiased and just gave basic definitions and examples of cancer treatments. I used the information to write about the traditional forms of cancer treatment.
Siegel, Mary-Ellen, M.S.W.. The Cancer Patient’s Handbook. New York: Walker and
• Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
Holder 13
Company,1986. This was a good source of information because it was especially written for cancer patients. Not only did it give possible side effects, but it also compared the kinds of treatments so patients know what they’re dealing with. I used this book as a compliment to Lisa Yount’s book.
“Melacine.” 15 January 2003
I used this website to learn about Melacine and what Corixa is doing. It was used in my report as an example of future monoclonal antibody drugs. I believe the information to be credible because it was given as a press release and the company presented facts and statistics to back its claims.
“BEXXAR.” 15 January 2003http://www.corixa.com/default.asp?pid=cancer_capsule&id=28.I used this website to learn about BEXXAR and what Corixa is doing. It was used in my report as an example of future immunotherapy drugs. I believe the information to be credible because it was given as a press release and the company presented facts and statistics to back its claims.
“Herceptin.” 20 January 2003
This source is credible because it was the company that makes the drug. It presented information in a factual way with statistics to back up its claims. I used this information as an example of immunological drugs already out on the market.
“RITUXAN” 20 January 2003.This source is credible because is not only because it was given by the company who makes RITUXAN, but it also gives detailed information as to the effects of the drug and the reasons it works (which check with my other research.) I used this information as an example of immunotherapy drugs already out on the market and approved by the FDA.
“Hotjobs” 25 January 2003http:www.hotjobs.com/cgi-bin/job-show?TEMPLATE=htdocs/job-show.html…I used this search engine to find a job description of a research associate. The job that matched my description was one at the John Wayne Cancer Institute in Santa Monica California. I feel that this is a credible source because it is a well known Cancer research program. I used the information I found as the majority of the descriptions of Research Associates in both my report and on my poster.
Johnson, Jeff. Personal Interview. February 18, 2003.Jeff Johnson was my mentor. He works at Corixa Corporation as a Senior Research Associate. His job, the fact that he was selected as a mentor through the Biotechnology Expo, and his education all contribute to his credibility. Currently he is working on the early stages of development/research of immunological therapies for cancer. My interview and my time spent with Jeff Johnson at Corixa Corporation is reflected in my report.
• Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
Holder 14
The Groundbreaking Career as aResearch Associate in Cancer Immunology
Journal• Ashley Holder • Grade 12 •
• Ms. Mary Glodowski • Juanita High School •• February 28, 2003 •
• Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
Holder 15
Notes
Research Associate in Cancer Immunology
Background/Training: ° College degree in Biological Science, Chemistry, Immunology, or Molecular Biology° Computer Knowledge° Experience in Radioisotopes° Experience with Tissue Culture° Column Chromatography° Protein Determinates° Immunoassay (ELISA, RIA, etc.)° Western Blots° Experience in Conduct of Pharmaceutical trials
Job Responsibilities:° Preparation and Isolation of Tumor Antigens from Biological Specimens to be used as Reagents to monitor Immune Responses of Cancer Patients’ Sera° Prepare Solutions° Perform Biochemical Analysis and Immunological Assays to monitor Antigens° Research/Develop various Immunological Assays using Reagents ° Record and Log Lab Equipment and Reagents as required for the General Laboratory Practices (GLP)
Typical Workday:° 9-5 job
Opportunities for Advancement:
• Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
Holder 16
° A Research Associate can become a Senior Research Associate when he/she has experience for a number of years as a member of a Clinical Team conducting Studies (Phase I-IV) according to Federal Regulations and ICH Guidelines. He/she as a Senior Research Associate, is responsible for writing or supervising the writing of Clinical Reports or Documents.
Salary Ranges:° $30-50 depending on area of country, experience, and company
What is Cancer?° Cells multiply wildly destroying healthy tissue° Occurs in both Plants and Animals° Occurs most often in middle-aged and elderly° Most affected areas = skin, digestive organs, lungs, prostate gland, female breasts.° Occurs when chemical instructions directing cell growth, are damaged and cells multiply w/o control° Caused by Genes (inherited) or Environment° Classified by Body Site and Tissue of Origin° Most Cancer is Carcinoma° Carcinoma = develops in epithelial tissue (Outer layer of skin and lines internal body surfaces and organs.° Sarcoma = develops in connective tissues
Genes Controlling Cell Growth and Division° Proto-oncogenes = promote cell growth/division° Suppressor genes = limit cell growth/division° When proto-oncogenes are damaged = over-active form called
oncogenes° Scientists have discovered dozens of oncogenes° When suppressor genes are damaged, the genes’ ability to stop cell multiplication is destroyed.
Traditional Cancer Treatments° Surgery° Radiation Therapy° Drugs (Chemotherapy)° Multimodality Therapy = Combo of treatments
Surgery° Take out tumor and possibly healthy tissue around tumor (like a mastectomy).
Radiation Therapy° Attacks w/x-rays or particles from radioactive substances like cobalt and radium° Negative Effect: Kills normal cells and cancer cells. To be positively effective, it must kill more cancer cells than normal° New Machines: Super-Voltage X-Ray and Cobalt Bomb that reduce the # of normal cells damaged.
Drug Therapy (Chemotherapy)
• Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
Holder 17
° Idea that drug can target cancer through a chemical process that doesn’t occur in normal cells.° Negative Effect: It damages normal cells that divide rapidly like cancer. These cells include blood-forming cells (Increase Risk of Infection), hair-forming cells (hair loss), and cells lining the intestines (nausea, vomiting).
Multimodality Therapy° Mixture of treatments can destroy undetected cancer cells in organs or other areas of body. ° A common combo is surgery and chemotherapy
Biological Response Modifiers° Increase body’s ability to fight cancer by strengthening natural responses° Some are Immunotherapies
° Stimulates Immune System to attack Cancer Cells° Others improve ability to withstand aggressive drug therapy
Biological Modifiers° Monoclonal Antibodies
° Immunotherapy° Anti-bodies (disease fighting proteins)° Thousands made by B-cell (White blood cell). They circulate in blood and bind to antigens (Foreign Substances).° When antibody attaches to antigen, marks it infected and destined for destruction.° Monoclonal Antibodies are made in a lab by combining cancer cell with B-cell. Produces antibodies that attach to cancer cells alerting the immune system to destroy the remaining cancer.° Positive: ideally won’t kill good cells
° Interferons° Protein produced by cells to resist infection by viruses° Has prevented reappearance of cancer
° Interleukin-2° Protein released by some white blood cells to support and sustain growth of other white blood cells.° Kidney Cancer: In some cancer patients, has stimulated growth of white blood cells that destroy cancer cells.
• Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
Holder 18
Interview
Q: What is your typical workday?
A: 10-20% Computer work and data analysis.
Q: How do Research Associates tie into the drug development process?
A: Research associates do the experiments and analyze results to give supervisors the
information the final decision as to where to go next. We basically do all the work!
Q: How did you decide to become a research associate?
A: Well, going to SPU, I didn’t get any financial aid, so I didn’t qualify for work-study
programs like most other people. To get in the door, my professor, Ken Moore, was able
to get me a job as a lab assistant at the Fred Hutchinson Cancer Research Center. I was
able to do my own research project and it just kind of took off from there.
We did not have a lengthy formal interview, but instead talked while I received a
tour of Corixa. My notes and impressions as well as my report reflect our rather
casual time together.
• Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
Holder 19
Impressions of Corixa and Mentorship
Experience
Arriving at Corixa, I was amazed at the amount of security. To get into the
building, I had to call the security desk for them to “buzz” me in. From there I went to
the second floor only to find another security measure. I was given a “Visitor” Badge in
exchange for my car keys and told to wait while my mentor, Jeff Johnson, was called.
As we made our way to Jeff Johnson’s work area, I was amazed at the company.
We passed through a hallway where the supervisors worked, (they had their own offices)
passed a group of men eating their lunches outside and entered the large room with 20
different lab/work stations. Everyone was diligently doing his or her research and
experiments. Shelves were labeled with employee names and chemicals and white lab
coats were flung over the backs of most seats.
We sat down at Jeff Johnson’s work area and I immediately noticed his open
container violations. I thought to myself, “Wow, Mrs. Glowdowski has taught me well!”
We started the interview, but weren’t really sure what to talk about. I asked the basic
questions, but we both lost interest quickly. At the end of the abbreviated interview, Mr.
Johnson gave me a tour of the lab. He showed me where the CHO was being processed
and the different floors. The lab areas on both floors were almost identical, except for the
personal touches of family portraits and pictures that adorned many workstations. Jeff
Johnson showed me the many cell samples and chemicals being kept in the refrigerators
and explained what their purposes were. He seemed impressed that I knew the basic ideas
• Ashley Holder • Grade 12 • Juanita High School • February 28, 2003
Holder 20
as to what he was explaining. Apparently, a couple of weeks earlier, he had had another
student who had not comprehended his explanations.
After learning the basics in the theory of cancer immunology, I was given the
opportunity to watch one of his experiments be processed. Jeff Johnson, his supervisor,
and I all went into a smaller room with a machine that processed some samples. The
cancer cells being processed were tested as to the substance that killed them.
Unfortunately, the results were not promising.
After the experiment was processed, I had to leave. Jeff Johnson showed me out
(I had no idea where I was and needed and employee card to get through most of the
doors) and we talked about college and things unrelated to cancer immunology.
Jeff Johnson was a great mentor. He, like most of the other employees at Corixa
Corporation, was very informative. He seemed to really love his job and was good at it.
• Ashley Holder • Grade 12 • Juanita High School • February 28, 2003